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Simultaneous MR imaging for tissue engineering in a rat model of stroke.

Nicholls FJ, Ling W, Ferrauto G, Aime S, Modo M - Sci Rep (2015)

Bottom Line: Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging.The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment.The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Pittsburgh, PA.

ABSTRACT
In situ tissue engineering within a stroke cavity is gradually emerging as a novel therapeutic paradigm. Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging. The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment. The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents. The development of sophisticated imaging methods is essential to guide delivery of the building blocks for in situ tissue engineering, but will also be essential to understand the dynamics of cellular interactions leading to the formation of de novo tissue.

No MeSH data available.


Related in: MedlinePlus

In vivo imaging of the distribution of implanted NSCs and ECs.(A) Pre-transplant baseline images indicated a few individual voxels with weak asymmetries at both 18 ppm (blue) and 97 ppm (red). Upon transplantation of unlabeled NSCs (160,000 cells) and ECs (40,000 cells), a few sporadic voxels could be observed, at similar levels to baseline. In contrast, upon implantation of Eu-HPDO3A and Yb-HPDO3A labeled NSCs and ECs, a clear localized signal at both 18 ppm and 97 ppm was evident with fewer unspecific voxels (due to better shimming to the actual signal). A T2 signal decrease was also evident due to the lanthanide complexes. Color-coded scale bars indicate % asymmetry. (B) These results are representative of all animals in both groups. In animals with labeled cells this afforded a visualization of the relative distribution of NSCs and ECs within the lesion cavity. In one animal, further unspecific signal at 97 ppm was observed highlighting the need for further improvements in paraCEST acquisition as well as image processing.
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f6: In vivo imaging of the distribution of implanted NSCs and ECs.(A) Pre-transplant baseline images indicated a few individual voxels with weak asymmetries at both 18 ppm (blue) and 97 ppm (red). Upon transplantation of unlabeled NSCs (160,000 cells) and ECs (40,000 cells), a few sporadic voxels could be observed, at similar levels to baseline. In contrast, upon implantation of Eu-HPDO3A and Yb-HPDO3A labeled NSCs and ECs, a clear localized signal at both 18 ppm and 97 ppm was evident with fewer unspecific voxels (due to better shimming to the actual signal). A T2 signal decrease was also evident due to the lanthanide complexes. Color-coded scale bars indicate % asymmetry. (B) These results are representative of all animals in both groups. In animals with labeled cells this afforded a visualization of the relative distribution of NSCs and ECs within the lesion cavity. In one animal, further unspecific signal at 97 ppm was observed highlighting the need for further improvements in paraCEST acquisition as well as image processing.

Mentions: To assess the potential of paraCEST to simultaneously visualize the distribution of NSCs and ECs in vivo, labeled and unlabeled cells were implanted into the stroke cavity of rats two weeks after middle cerebral artery occlusion (MCAO) surgery. Pre-transplant a few unspecific voxels were apparent (Fig. 6A). After transplantation of unlabeled cells, a few sporadic voxels exhibiting MT effects were evident. Implantation of paraCEST-labeled cells in contrast resulted in a dramatic decrease in T2 in the area of transplantation, but also produced a robust signal at 18 ppm (Eu-HPDO3A) and 97 ppm (Yb-HPDO3A) at the site of implantation. Although a homogenously mixed population of NSCs and ECs was implanted, regional differences in distribution were apparent after 24 hours survival. This pattern of in vivo representation of the distribution of NSCs and ECs was apparent in all 3 animals indicating the reproducibility of this approach (Fig. 6B). However, it is noteworthy that in one subject (rat 2), a significant number of unspecific voxels at 97 ppm were detected. It is important to note that a lack of signal in a region, does not necessarily imply the absence of one particular cell type, but is likely a reflection of certain regions having more cells than other regions. The average signal difference between labeled and unlabeled cells in the lesion cavity was 3.27% ± 0.78 (p < 0.05) for Eu-HPDO3A and 1.16% ± 0.19 (p < 0.01) for Yb-HPDO3A. From the overlay images, it is also apparent that implantation of an NSC/EC mix did not sufficiently disperse to cover the stroke-damaged area.


Simultaneous MR imaging for tissue engineering in a rat model of stroke.

Nicholls FJ, Ling W, Ferrauto G, Aime S, Modo M - Sci Rep (2015)

In vivo imaging of the distribution of implanted NSCs and ECs.(A) Pre-transplant baseline images indicated a few individual voxels with weak asymmetries at both 18 ppm (blue) and 97 ppm (red). Upon transplantation of unlabeled NSCs (160,000 cells) and ECs (40,000 cells), a few sporadic voxels could be observed, at similar levels to baseline. In contrast, upon implantation of Eu-HPDO3A and Yb-HPDO3A labeled NSCs and ECs, a clear localized signal at both 18 ppm and 97 ppm was evident with fewer unspecific voxels (due to better shimming to the actual signal). A T2 signal decrease was also evident due to the lanthanide complexes. Color-coded scale bars indicate % asymmetry. (B) These results are representative of all animals in both groups. In animals with labeled cells this afforded a visualization of the relative distribution of NSCs and ECs within the lesion cavity. In one animal, further unspecific signal at 97 ppm was observed highlighting the need for further improvements in paraCEST acquisition as well as image processing.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588587&req=5

f6: In vivo imaging of the distribution of implanted NSCs and ECs.(A) Pre-transplant baseline images indicated a few individual voxels with weak asymmetries at both 18 ppm (blue) and 97 ppm (red). Upon transplantation of unlabeled NSCs (160,000 cells) and ECs (40,000 cells), a few sporadic voxels could be observed, at similar levels to baseline. In contrast, upon implantation of Eu-HPDO3A and Yb-HPDO3A labeled NSCs and ECs, a clear localized signal at both 18 ppm and 97 ppm was evident with fewer unspecific voxels (due to better shimming to the actual signal). A T2 signal decrease was also evident due to the lanthanide complexes. Color-coded scale bars indicate % asymmetry. (B) These results are representative of all animals in both groups. In animals with labeled cells this afforded a visualization of the relative distribution of NSCs and ECs within the lesion cavity. In one animal, further unspecific signal at 97 ppm was observed highlighting the need for further improvements in paraCEST acquisition as well as image processing.
Mentions: To assess the potential of paraCEST to simultaneously visualize the distribution of NSCs and ECs in vivo, labeled and unlabeled cells were implanted into the stroke cavity of rats two weeks after middle cerebral artery occlusion (MCAO) surgery. Pre-transplant a few unspecific voxels were apparent (Fig. 6A). After transplantation of unlabeled cells, a few sporadic voxels exhibiting MT effects were evident. Implantation of paraCEST-labeled cells in contrast resulted in a dramatic decrease in T2 in the area of transplantation, but also produced a robust signal at 18 ppm (Eu-HPDO3A) and 97 ppm (Yb-HPDO3A) at the site of implantation. Although a homogenously mixed population of NSCs and ECs was implanted, regional differences in distribution were apparent after 24 hours survival. This pattern of in vivo representation of the distribution of NSCs and ECs was apparent in all 3 animals indicating the reproducibility of this approach (Fig. 6B). However, it is noteworthy that in one subject (rat 2), a significant number of unspecific voxels at 97 ppm were detected. It is important to note that a lack of signal in a region, does not necessarily imply the absence of one particular cell type, but is likely a reflection of certain regions having more cells than other regions. The average signal difference between labeled and unlabeled cells in the lesion cavity was 3.27% ± 0.78 (p < 0.05) for Eu-HPDO3A and 1.16% ± 0.19 (p < 0.01) for Yb-HPDO3A. From the overlay images, it is also apparent that implantation of an NSC/EC mix did not sufficiently disperse to cover the stroke-damaged area.

Bottom Line: Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging.The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment.The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiology, Pittsburgh, PA.

ABSTRACT
In situ tissue engineering within a stroke cavity is gradually emerging as a novel therapeutic paradigm. Considering the varied lesion topology within each subject, the placement and distribution of cells within the lesion cavity is challenging. The use of multiple cell types to reconstruct damaged tissue illustrates the complexity of the process, but also highlights the challenges to provide a non-invasive assessment. The distribution of implanted cells within the lesion cavity and crucially the contribution of neural stem cells and endothelial cells to morphogenesis could be visualized simultaneously using two paramagnetic chemical exchange saturation transfer (paraCEST) agents. The development of sophisticated imaging methods is essential to guide delivery of the building blocks for in situ tissue engineering, but will also be essential to understand the dynamics of cellular interactions leading to the formation of de novo tissue.

No MeSH data available.


Related in: MedlinePlus